LET-413/Erbin acts as a RAB-5 effector to promote RAB-10 activation during endocytic recycling

The Journal of Cell Biology
Hang LiuAnbing Shi

Abstract

RAB-10/Rab10 is a master regulator of endocytic recycling in epithelial cells. To better understand the regulation of RAB-10 activity, we sought to identify RAB-10(GDP)-interacting proteins. One novel RAB-10(GDP)-binding partner that we identified, LET-413, is the Caenorhabditis elegans homologue of Scrib/Erbin. Here, we focus on the mechanistic role of LET-413 in the regulation of RAB-10 within the C. elegans intestine. We show that LET-413 is a RAB-5 effector and colocalizes with RAB-10 on endosomes, and the overlap of LET-413 with RAB-10 is RAB-5 dependent. Notably, LET-413 enhances the interaction of DENN-4 with RAB-10(GDP) and promotes DENN-4 guanine nucleotide exchange factor activity toward RAB-10. Loss of LET-413 leads to cytosolic dispersion of the RAB-10 effectors TBC-2 and CNT-1. Finally, we demonstrate that the loss of RAB-10 or LET-413 results in abnormal overextensions of lateral membrane. Hence, our studies indicate that LET-413 is required for DENN-4-mediated RAB-10 activation, and the LET-413-assisted RAB-5 to RAB-10 cascade contributes to the integrity of C. elegans intestinal epithelia.

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Citations

Dec 20, 2018·Frontiers in Cell and Developmental Biology·Pero LučinStipan Jonjić
Jan 2, 2019·The Journal of Cell Biology·Teresa T Bonello, Mark Peifer
May 9, 2019·Cell and Tissue Research·Ivan Dimov, Morris F Maduro
Aug 29, 2019·Annual Review of Cell and Developmental Biology·Melissa A PickettJessica L Feldman
Mar 23, 2018·The Journal of Cell Biology·Dan ChenAnbing Shi
Oct 2, 2020·Oncogene·Marie-Josée SantoniJean-Paul Borg
Sep 11, 2020·Journal of Developmental Biology·Matthew BuechnerHikmat Al-Hashimi
Apr 20, 2021·Biogerontology·Foteini AktypiNiki Chondrogianni

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Methods Mentioned

BETA
GTPases
GTPase
nucleotide exchange
pull-down
transgenic
biosensor
pull down
PCR
transfection
in vitro transcription

Software Mentioned

Metamorph
GraphPad
Prism
Elements AR
Fiji ( ImageJ
NIS

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